M2 muscarinic receptors in pontine reticular formation of C57BL/6J mouse contribute to rapid eye movement sleep generation

Coleman, Christal G.; Lydic, Ralph; Baghdoyan, Helen A.

doi:10.1016/j.neuroscience.2004.04.029

Cited by 54 publications

(47 citation statements)

References 64 publications

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“…They showed an increase of the number of REMs and REM sleep maintenance after the administration of numerous ACh-esterase inhibitors. Also, preclinical (Velazquez-Moctezuma et al, 1991;Coleman et al, 2004) and clinical (Riemann et al, 1988;Gillin et al, 1991) studies have shown that compounds with a selective affinity for M 1 mAChRs did not affect these parameters. In contrast, the ACh-esterase inhibitor tacrin did not significantly affect REM density or duration (Riemann et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the frequently used parameter REM density is less adequate to reflect alterations in the generation of REMs itself since it depends on the REM sleep duration. Given that the M 1 and M 2 mAChR subtype are the most abundant AChR subtypes in the mammalian cortex (Levey et al, 1991), and given that there is broad evidence from preclinical studies indicating that the number of REMs and REM maintenance are predominantly mediated by M 2 mAChR activity in the brain stem (VelazquezMoctezuma et al, 1991;Coleman et al, 2004), it is likely to assume that the increases in the number of REMs and REM sleep duration observed after the administration of donepezil in the present study are mediated, to a large extent, by M 2 mAChR activation at the brain stem level.…”

Section: Discussionmentioning

confidence: 99%

“…Microinjecting the ACh-esterase inhibitor neostigmine into medial regions of the mouse PRF causes a REM sleep-like state that is blocked by the M 2 /M 4 antagonist methoctramine but not by the M 1 /M 4 antagonist pirenzepine, indicating M 2 mAChR mediation (Coleman et al, 2004). Additionally, the M 3 mAChR subtype in the perilocus coeruleus alpha region of the cat pons contributed to REM sleep generation (Sakai and Onoe, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Nissen

Nofzinger

Feige

et al. 2005

Neuropsychopharmacol

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Broad evidence from preclinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the generation of rapid eye movement (REM) sleep. However, a potential role of different acetylcholine receptor (AChR) subtypes for the regulation of three main aspects of REM sleep, (1) REM onset, (2) REM maintenance, and (3) generation of REMs, are not clear. In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M 1 muscarinic AChR (mAChR) agonist RS-86 and the ACh-esterase inhibitor donepezil to further specify the AChR subtype function on REM sleep regulation in n ¼ 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p ¼ 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p ¼ 0.000 compared to placebo; p ¼ 0.003 compared to RS-86) and the number of REMs (p ¼ 0.000 compared to placebo; p ¼ 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M 1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M 1 , but presumably M 2 mAChR activity. These findings are of interest for the understanding of sleep regulation and of neuropsychiatric disorders, such as Alzheimer's dementia and depressive disorders, whose etiopathology may involve alterations in cholinergic neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Nissen

Nofzinger

Feige

et al. 2005

Neuropsychopharmacol

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show abstract

“…This enhanced facilitation could reflect a cholinergic hypersensitivity at the level of pontine REM sleep control system (Gillin et al, 1991;Seifritz et al, 1998). Along this line, the larger amounts of Sleep regulation in helpless mice D Popa et al REM sleep in H mice under baseline conditions might be explained, at least in part, by a high muscarinic tone (Coleman et al, 2004), just as in the case of FSL (Flinders Sensitive Line) rats, another validated model of depression (Overstreet, 1993).…”

Section: Muscarinic-and 5-ht 1a -Receptor-mediated Regulations Of Remmentioning

confidence: 99%

“…In particular, REM sleep is enhanced following treatments with cholinergic agonists in rats (Baghdoyan, 1997), mice (Coleman et al, 2004), and humans (Seifritz et al, 1998;Sitaram and Gillin, 1980). In contrast, REM sleep is inhibited by 5-HT 1A agonists (Boutrel et al, 1999;Driver et al, 1995;Tissier et al, 1993).…”

Section: Muscarinic-and 5-ht 1a -Receptor-mediated Regulations Of Remmentioning

confidence: 99%

Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation

Popa

Yacoubi²,

Vaugeois³

et al. 2005

Neuropsychopharmacol

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In depressed patients, sleep undergoes marked alterations, especially sleep onset insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM) sleep. Abnormalities of rest-activity rhythms and of hypothalamic-pituitary-adrenocortical function have also been described in these patients. In the present study, we examined the presence of such abnormalities in a recently developed line of mice (Helpless mice-H) that exhibit depression-like behaviors in validated tests, compared to the nonhelpless (NH) line derived from the same colony. Experiments were essentially carried out in females for which previous studies showed marked differences between H and NH lines. Compared to NH mice, the H line exhibited (i) lower basal locomotor activity, (ii) sleep fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep reflected by increased amounts and decreased latency, (iii) larger response to the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline). In contrast, H and NH mice were equally responsive to the REM sleep inhibitory effect of 5-HT 1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency in delta power enhancement after sleep deprivation was observed in the H group, and acute immobilization stress in this group failed to elicit a REM sleep rebound and was associated with a long-lasting raise in serum corticosterone levels. These results further validate H mice as a depression model and suggest they might be of particular interest for investigating the neurobiological mechanisms and possibly genetic substrates underlying sleep alterations associated with depression.

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Rapid analysis of neurotransmitters in rat brain using ultra‐fast liquid chromatography and tandem mass spectrometry: application to a comparative study in normal and insomnic rats

Jia

et al. 2013

J. Mass. Spectrom.

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Neurotransmitters and their metabolites in central nervous system were known to play a significant role in sedation and hypnosis. A rapid and sensitive UFLC-MS/MS method for simultaneous determination of serotonin, 5-hydroxyindole acetic acid (5-HIAA), tryptophan (Try), dopamine (DA), norepinephrine (NE), γ-aminobutyric acid (GABA), glutamic acid (Glu) and acetylcholine (Ach) in rat brain without derivatization, ion-pairing reagent or pre-concentration was developed. Analytes and IS were separated on a Inertsil ODS-EP column (150 mm × 4.6 mm, 5 µm particles) and analyzed in a single chromatographic run in less than 9.0 min, using gradient elution with the mobile phase consisting of methanol and 0.01% acetic acid in water at a flow rate of 1.2 ml min(-1) . The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in positive ion and multiple reaction monitoring mode. The developed method provided excellent linear calibration curves for the assay of analytes (R(2) ≥ 0.9915). Limits of quantification were in the range of 1.0 ng ml(-1) to 1.0 µg ml(-1) for the analytes in rat brain. Intra- and inter-day precision and accuracy of analytes were well within acceptance criteria (15%). Mean extraction recoveries of analytes and IS from rat brain were all more than 80.0%. Furthermore, the validated method was successfully applied to comparing profiles of analytes in normal and insomnic rat brains. Results indicated that there were statistically significant differences for serotonin, 5-HIAA, DA, NE, Glu and Ach, but no significant difference for Try and GABA between two groups.

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M2 muscarinic receptors in pontine reticular formation of C57BL/6J mouse contribute to rapid eye movement sleep generation

Cited by 54 publications

References 64 publications

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation

Rapid analysis of neurotransmitters in rat brain using ultra‐fast liquid chromatography and tandem mass spectrometry: application to a comparative study in normal and insomnic rats

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